Abstract:

Background: Amyloid-beta (Aβ) induced mitochondrial dysfunction is one of the major
causes of neuronal toxicity in Alzheimer’s disease. A number of recent reports suggest involvement of
mitochondrial alterations through intracellular accumulation of oligomeric Aβ. These mitochondrial alterations
include increased Reactive Oxygen Species (ROS), mt-DNA depletion, decreased oxidative
phosphorylation and ATP production, membrane depolarization, reduced number of mitochondria etc.
All these defects cumulatively caused neural toxicity and alterations in cellular energy homeostasis. On
the other hand, anti-inflammatory drug aspirin is reported to promote both mitochondrial biogenesis and
improvement in cellular energy status.

Methods: Taking altogether the mentioned clues, we evaluated protective effect of aspirin, if any on oligomeric
Aβ42 induced toxicity and mitochondrial alterations in differentiated neuronal cells.

Results: A significant reduction in neuronal viability and increased apoptosis was observed in Aβ42
treated cells, as evident by MTT assay, apoptosis ELISA and immunofluorescence from β-III tubulin
antibody staining of neuronal cells. A concomitant decrease was also observed in the intensity of mitotracker
red FM staining and mt-DNA to nDNA ratio, suggesting mitochondrial membrane depolarization
and/or reduced number of mitochondria along with depletion in mt-DNA. However, simultaneous
treatment of 5 μM aspirin to oligomeric Aβ42 treated cells protected them from mitochondrial dysfunction
and neurotoxicity.

Conclusion: We suggest mitochondrial biogenesis, changes in mitochondrial membrane potential and /
or inhibition of Aβ42 aggregation by aspirin as possible underlying mechanism(s).

Abstract:Background: Amyloid-beta (Aβ) induced mitochondrial dysfunction is one of the major
causes of neuronal toxicity in Alzheimer’s disease. A number of recent reports suggest involvement of
mitochondrial alterations through intracellular accumulation of oligomeric Aβ. These mitochondrial alterations
include increased Reactive Oxygen Species (ROS), mt-DNA depletion, decreased oxidative
phosphorylation and ATP production, membrane depolarization, reduced number of mitochondria etc.
All these defects cumulatively caused neural toxicity and alterations in cellular energy homeostasis. On
the other hand, anti-inflammatory drug aspirin is reported to promote both mitochondrial biogenesis and
improvement in cellular energy status.

Methods: Taking altogether the mentioned clues, we evaluated protective effect of aspirin, if any on oligomeric
Aβ42 induced toxicity and mitochondrial alterations in differentiated neuronal cells.

Results: A significant reduction in neuronal viability and increased apoptosis was observed in Aβ42
treated cells, as evident by MTT assay, apoptosis ELISA and immunofluorescence from β-III tubulin
antibody staining of neuronal cells. A concomitant decrease was also observed in the intensity of mitotracker
red FM staining and mt-DNA to nDNA ratio, suggesting mitochondrial membrane depolarization
and/or reduced number of mitochondria along with depletion in mt-DNA. However, simultaneous
treatment of 5 μM aspirin to oligomeric Aβ42 treated cells protected them from mitochondrial dysfunction
and neurotoxicity.

Conclusion: We suggest mitochondrial biogenesis, changes in mitochondrial membrane potential and /
or inhibition of Aβ42 aggregation by aspirin as possible underlying mechanism(s).